LoViReT (Low Viral Reservoir Treated Patients)

NCT02972931 | Completed Results

• 1 other identifier: LoViReT
• Study Type: observational
• Target: 62
• Locations: 1 country
• Sites: 1

Brief Summary

The main purpose of this study is to unravel the mechanisms by which the "Low Viral Reservoir Treated" patients (LoViReT) maintain extremely low HIV-1 DNA levels despite having initiated cART during chronic HIV-1 infection. This group may have specific and different clinical, virological and immunogenetical characteristics, compared to patients with regular reservoir size, which might be useful to design new and more effective treatment approaches.

Conditions

Hiv

Keywords

HIV infection; low HIV reservoir; functional cure

Outcome Measures

Primary Outcomes (5)

• Longitudinal Analysis of Total HIV DNA and Immune-phenotype by Digital Droplet Polymerase Chain Reaction (PCR) and Flow Cytometry, Respectively, Comparing This Outcome Before and After cART (Evaluation of cART Effect on This Parameters)

  To address this objective, a longitudinal analysis of proviral HIV DNA for each patient will be performed, including time points previous to cART. In total, 200 samples will be analyzed and dynamic models will be built for the two different levels of reservoir establishment. General immune phenotype of cellular populations, including also activation markers, will be also assessed in all time points.

  The time frame for the outcome measure is an average of 5 years. Including a baseline, 18 months, and 5 years post cART initiation.

• Replication Competent Reservoir in Patients With Low (LoViReT) Normal (Controls) Levels of Total HIV DNA

  Replication competent reservoir will be analyzed with the gold standard quantitative viral outgrowth assay (qVOA).

  The time frame for the outcome measure is on patients on cART for at least 5 years.

• Evaluation and Comparison of CD8 T-cell Responses by Inhibition Assays, Between Patients With Low (LoViReT) and Normal (Controls) Levels of Total HIV DNA

  Functional T-cell response will be measured isolating CD8 T and Nk cells and measuring the inhibition capacity for HIV replication in each patient.

  The time frame for the outcome measure is on samples before initiation of cART and after 5 years on cART

• Analysis and Comparison of Progression-associated Genetic Factors, Between Patients With Low (LoViReT) and Normal (Controls) Levels of Total HIV DNA

  Different progression-associated genetic factors, such as HLA type, and CCR5, CCR2 and SIGLEC-1 single nucleotide polymorphisms (SNPs) will be also explored.

  The time frame for the outcome measure is on patients on cART for at least 5 years.

• Measurement of Genotypic Tropism in Patients With Low (LoViReT) and Normal (Controls) Levels of Total HIV DNA

  Genotypic HIV tropism and the full viral genome will be analyzed through sequencing from DNA of patients' peripheral blood mononuclear cells (PBMC).

  The time frame for the outcome measure is on patients on cART for at least 5 years.

Study Arms (2)

LoViReT

HIV-infected subjects with extremely low or undetectable HIV-1 DNA levels in peripheral blood despite having initiated cART during chronic HIV-1 infection

Standard Reservoir Level

HIV-infected subjects who initiated cART during chronic HIV-1 infection and that show standard HIV-1 DNA levels in peripheral blood

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

HIV-infected subjects with extremely low or undetectable HIV-1 DNA levels in peripheral blood despite having initiated cART during chronic HIV-1 infection

You may qualify if:

• ≥ 18 years of age
• Voluntarily signed informed consent
• Proven HIV-1 infection
• On stable cART regimen (antiretroviral therapy consisting of at least 3 registered antiretroviral agents) for at least 3 years
• HIV-RNA \<50 copies/mL during the last 3 years prior to the study
• Proviral HIV-DNA \<50 copies/million PBMCs by using the ultrasensitive BioRad residual ddPCR quantification platform

You may not qualify if:

• cART discontinuation between previous screening and Visit #1.
• HIV-RNA above 50 copies/mL between previous screening to Visit #1

Sponsors & Collaborators

• IrsiCaixa: lead

Study Sites (1)

Hospital Universitari Germans Trias i Pujol

Badalona, Barcelona, 08916, Spain

Location

Related Publications (2)

• Galvez C, Urrea V, Dalmau J, Jimenez M, Clotet B, Monceaux V, Huot N, Leal L, Gonzalez-Soler V, Gonzalez-Cao M, Muller-Trutwin M, Saez-Cirion A, Garcia F, Blanco J, Martinez-Picado J, Salgado M. Extremely low viral reservoir in treated chronically HIV-1-infected individuals. EBioMedicine. 2020 Jul;57:102830. doi: 10.1016/j.ebiom.2020.102830. Epub 2020 Jun 21.

  PMID: 32580136 BACKGROUND

• Galvez C, Urrea V, Garcia-Guerrero MDC, Bernal S, Benet S, Mothe B, Bailon L, Dalmau J, Martinez A, Nieto A, Leal L, Garcia F, Clotet B, Martinez-Picado J, Salgado M. Altered T-cell subset distribution in the viral reservoir in HIV-1-infected individuals with extremely low proviral DNA (LoViReTs). J Intern Med. 2022 Aug;292(2):308-320. doi: 10.1111/joim.13484. Epub 2022 Mar 28.

  PMID: 35342993 BACKGROUND

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome; HIV Infections

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Limitations and Caveats

As expected and included in the protocol, not all participants were willing to provide all the types of samples, but relevant results were obtained anyway.

Results Point of Contact

• Title: Dr. Judith Dalmau
• Organization: AIDS Research Institute IrsiCaixa

jdalmau@irsicaixa.es

934656374

Study Officials

• Javier Martinez-Picado, PhD

  IrsiCaixa AIDS Research Institute, Hospital Universitari Germans Trias i Pujol

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 17, 2016
• First Posted: November 25, 2016
• Study Start: January 18, 2018
• Primary Completion: June 20, 2019
• Study Completion: June 20, 2019
• Last Updated: September 19, 2024
• Results First Posted: September 19, 2024

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)